Rambousek Lukas, Kacer Petr, Syslova Kamila, Bumba Jakub, Bubenikova-Valesova Vera, Slamberova Romana
Institute of Chemical Technology, Technicka 5, Prague 166 28, Czech Republic; Institute of Physiology AS CR v.v.i., Videnska 1083, Prague 142 20, Czech Republic.
Institute of Chemical Technology, Technicka 5, Prague 166 28, Czech Republic.
Drug Alcohol Depend. 2014 Jun 1;139:138-44. doi: 10.1016/j.drugalcdep.2014.03.023. Epub 2014 Mar 29.
Methamphetamine (METH) abuse is a growing health problem worldwide, and METH use during pregnancy not only endangers the mother's health but also the developing fetus. To provide better insight into these risks, we performed the following experiments.
First, we investigated how sex influences the pharmacokinetics of METH and amphetamine (AMP) in male and female rats. Subsequently, we simulated chronic exposure of prenatal infants to METH abuse by investigating brain and plasma levels of METH and AMP in dams and pups. Finally, we modeled chronic exposure of infants to METH via breast milk and investigated sex differences in pups with regard to drug levels and possible sensitization effect of chronic prenatal METH co-treatment.
We observed significantly higher levels of METH and AMP in the plasma and brain of female rats compared to males. Additionally, brain concentrations of METH and AMP in pups exposed to METH prenatally were equivalent to 62.13% and 37.78% relative to dam, respectively. Plasma concentrations of AMP where equivalent to 100% of the concentration in dams, while METH was equivalent to only 36.98%. Finally, we did not observe a significant effect relative to sex with regard to METH/AMP levels or sensitization effects linked to prenatal METH exposure.
We demonstrated that female rats display higher levels of METH and AMP, thus indicating a greater risk of addiction and toxicity. Furthermore, our data show that pups are exposed to both METH and AMP following dam exposure.
甲基苯丙胺（METH）滥用在全球范围内是一个日益严重的健康问题，孕期使用甲基苯丙胺不仅危及母亲健康，还会影响发育中的胎儿。为了更深入了解这些风险，我们进行了以下实验。
首先，我们研究了性别如何影响雄性和雌性大鼠体内甲基苯丙胺和苯丙胺（AMP）的药代动力学。随后，我们通过研究母鼠和幼崽体内甲基苯丙胺和苯丙胺的脑内及血浆水平，模拟了产前婴儿长期暴露于甲基苯丙胺滥用的情况。最后，我们建立了婴儿通过母乳长期暴露于甲基苯丙胺的模型，并研究了幼崽在药物水平方面的性别差异以及产前甲基苯丙胺联合治疗可能产生的致敏作用。
我们观察到，与雄性大鼠相比，雌性大鼠血浆和脑内的甲基苯丙胺和苯丙胺水平显著更高。此外，产前暴露于甲基苯丙胺的幼崽脑内甲基苯丙胺和苯丙胺浓度分别相当于母鼠的62.13%和37.78%。血浆中苯丙胺浓度相当于母鼠浓度的100%，而甲基苯丙胺仅相当于36.98%。最后，我们未观察到甲基苯丙胺/苯丙胺水平或与产前甲基苯丙胺暴露相关的致敏作用在性别方面有显著影响。
我们证明雌性大鼠体内甲基苯丙胺和苯丙胺水平更高，这表明其成瘾和中毒风险更大。此外，我们的数据表明，母鼠暴露后，幼崽会接触到甲基苯丙胺和苯丙胺。
